UA Faculty Publicationshttp://hdl.handle.net/10150/595893
Tue, 18 Dec 2018 01:26:14 GMT2018-12-18T01:26:14ZA catalogue of somatic NRF2 gain-of-function mutations in cancerhttp://hdl.handle.net/10150/631217
A catalogue of somatic NRF2 gain-of-function mutations in cancer
Kerins, Michael John; Ooi, Aikseng
Identification and characterization of somatic mutations in cancer have important prognostication and treatment implications. Genes encoding the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcription factor and its negative regulator, Kelch-like ECH-associated protein 1 (KEAP1), are frequently mutated in cancer. These mutations drive constitutive NRF2 activation and correlate with poor prognosis. Despite its apparent significance, a comprehensive catalogue of somatic NRF2 mutations across different tumor types is still lacking. Here, we catalogue NRF2 mutations in The Cancer Genome Atlas (TCGA) database. 226 unique NRF2-mutant tumors were identified from 10,364 cases. NRF2 mutations were found in 21 out of the 33 tumor types. A total of 11 hotspots were identified. Of these, mutation to the R34 position was most frequent. Notably, R34 and D29 mutations were overrepresented in bladder, lung, and uterine cancers. Analyses of corresponding RNA sequencing data using a de novo derived gene expression classifier showed that the R34 mutations drive constitutive NRF2 activation with a selection pressure biased against the formation of R34L. Of all R34 mutants, R34L conferred the least degree of protein stabilization, suggesting a pro-tumor NRF2 half-life threshold. Our findings offer a comprehensive catalogue of NRF2 mutations in cancer that can help prognostication and NRF2 research.
Mon, 27 Aug 2018 00:00:00 GMThttp://hdl.handle.net/10150/6312172018-08-27T00:00:00ZThe associations between anthropometric measurements and left ventricular structure and function: the Echo-SOL Studyhttp://hdl.handle.net/10150/631216
The associations between anthropometric measurements and left ventricular structure and function: the Echo-SOL Study
Ponce, S.; Allison, M. A.; Swett, K.; Cai, J.; Desai, A. A.; Hurwitz, B. E.; Ni, A.; Schneiderman, N.; Shah, S. J.; Spevack, D. M.; Talavera, G. A.; Rodriguez, C. J.
Objective The objective of this study is to determine associations between anthropometry and echocardiographic measures of cardiac structure and function in Hispanic/Latinos. Methods A total of 1,824 participants from ECHO-SOL were included. We evaluated associations between echocardiographic measures of left ventricular structure and function and anthropometric measures using multivariable-adjusted linear and logistic regression models adjusting for traditional cardiovascular risk factors. Results The mean age was 560.17years, 57% were women. The mean body mass index (BMI) was 30 +/- 9.4kgm(-2), waist circumference (WC) was 100 +/- 18cm, and waist-to-hip ratio (WHR) was 0.93 +/- 0.15. Adjusted analysis showed that 5-unit increment in BMI and 5-cm increase in WC was associated with 3.4 +/- 0.6 and 1.05 +/- 0.05gm(-2.7) (p<0.05 for both) higher left ventricular (LV) mass index, respectively. Similarly, 0.1-unit increment in WHR was associated with 2.0 +/- 0.16gm(-2.7) higher LV mass index (p<0.01). WHR was associated with 0.22 +/- 0.08% decrease in ejection fraction (p<0.05). Concomitantly, 5-unit increment in BMI and WC was associated with increased odds of abnormal LV geometry (odds ratio 1.40 and 1.16, p=0.03 and <0.01, respectively); 0.1-unit increment in WHR was associated with increased odds of abnormal LV geometry (odds ratio 1.51, p<0.01). Conclusions Among Hispanic/Latinos, higher anthropometric measures were associated with adverse cardiac structure and function.
Wed, 01 Aug 2018 00:00:00 GMThttp://hdl.handle.net/10150/6312162018-08-01T00:00:00ZQuantifying human-environment interactions using videography in the context of infectious disease transmissionhttp://hdl.handle.net/10150/631215
Quantifying human-environment interactions using videography in the context of infectious disease transmission
Julian, Timothy R.; Bustos, Carla; Kwong, Laura H.; Badilla, Alejandro D.; Lee, Julia; Bischel, Heather N.; Canales, Robert A.
Quantitative data on human-environment interactions are needed to fully understand infectious disease transmission processes and conduct accurate risk assessments. Interaction events occur during an individual's movement through, and contact with, the environment, and can be quantified using diverse methodologies. Methods that utilize videography, coupled with specialized software, can provide a permanent record of events, collect detailed interactions in high resolution, be reviewed for accuracy, capture events difficult to observe in real-time, and gather multiple concurrent phenomena. In the accompanying video, the use of specialized software to capture human-environment interactions for human exposure and disease transmission is highlighted. Use of videography, combined with specialized software, allows for the collection of accurate quantitative representations of human-environment interactions in high resolution. Two specialized programs include the Virtual Timing Device for the Personal Computer, which collects sequential microlevel activity time series of contact events and interactions, and LiveTrak, which is optimized to facilitate annotation of events in real-time. Opportunities to annotate behaviors at high resolution using these tools are promising, permitting detailed records that can be summarized to gain information on infectious disease transmission and incorporated into more complex models of human exposure and risk.
Mon, 01 Jan 2018 00:00:00 GMThttp://hdl.handle.net/10150/6312152018-01-01T00:00:00ZNomenclature Wars: Ethnologists and Anthropologists Seeking to Be Scientists, 1840–1910http://hdl.handle.net/10150/631214
Nomenclature Wars: Ethnologists and Anthropologists Seeking to Be Scientists, 1840–1910
Fowler, Don D.; Parezo, Nancy J.
Scholarly disciplines are ever-changing and continuously debated constellations of intellectual heritage and contemporary issues. This article discusses debates over anthropological nomenclature, anthropometric indices, and museum exhibit design in the development of European and American anthropology from its ethnological beginnings in the 1840s through nineteenth-century evolutionism to the establishment of the Boasian historical particularist approach after 1904. It also outlines the impacts of those debates and disagreements on the subsequent development of the "four-field approach" in American-university-based anthropology programs. The transitions from ethnology to evolutionism to particularism can be followed through arguments over nomenclature, anthropometrics, and the content and design of museum exhibits, as nascent anthropologists defined and redefined their subfield(s) of study and attempted to become part of the burgeoning Science Establishment of the nineteenth and early twentieth centuries in Europe and North America. The arguments and their (sometimes) resolutions laid the foundations for twentieth-century university-based anthropology programs and ethnographic and archaeological exhibits in anthropology and natural history museums. The article is, thus, a contribution to the developmental history of anthropology in Europe and North America.
Mon, 30 Jul 2018 00:00:00 GMThttp://hdl.handle.net/10150/6312142018-07-30T00:00:00Z